Microfluidic technology has attracted interest for biotechnology and pharmaceutical applications, including drug screening and toxicology testing. Microfluidics refers to the design of systems in which small volumes (e.g., μL, nL, pL or fL) of fluids are moved or otherwise handled. For example, one or more microfluidic channels or network of channels may be used to direct flow of fluids in a device, wherein cellular, chemical or molecular processes or reactions take place in the channels by virtue of the fluidic properties of the channels. The term “microfluidic” typically refers to fluids provided to channels having internal dimensions of between about 0.1 and 500 μm.
Microfluidic platforms have been studied for use in vascular applications at least in part because they can be configured to facilitate predictable flow characteristics and physiologically relevant dimensions. For example, single channel microfluidic devices have been used to examine endothelial cell adhesion (Young et al. Lab on a Chip 2007; 7:1759-1766) and endothelial drug permeability (Young et al. Analytical Chemistry 2010; 82:808-816), and to demonstrate monocyte adhesion and transmigration through endothelium (Srigunapalan et al. Biomicrofluidics 2011; 5:13409). Flow-regulated paracrine interactions between an endothelial monolayer and myofibroblasts embedded in a 3D “microtissue” hydrogel have also been examined in a single microchannel platform (Chen et al. Lab on a Chip 2013; 13:2591-8). However, single microchannel platforms are not suitable for many biotechnology and pharmaceutical applications, which require medium- to high-throughput capacity.
Microfluidic platforms configured for medium- to high-throughput use are known. For example, devices described in PCT/US2009/00045, PCT/US2010/043743 and Meyvantsson et al. (Lab on a Chip 2008; 8:717-724) were designed for used in cell-based flow assays. However, these devices use passive flow mechanisms (e.g., capillary or gravity driven flow), which do not mimic physiological flow forces, such as those in blood vessels. The 24-well BioFlux system (Conant et al. Biotechnol Bioeng 2011; 108:2978-87) has been used to study the effects of flow on a monolayer of endothelial cells in two dimensions. However, the BioFlux system requires complex and proprietary machinery and vast networks of tubing that are incompatible with standard robotic liquid handling systems and standard microplate readers, hindering their use for medium- to high-throughput drug and toxicology screening. Further, none of the aforementioned medium- to high-throughput devices mimic three-dimensional vascularized tissues, which facilitate interaction of multiple cell types interacting in a physiologically relevant manner.
Co-culture microfluidic devices capable of mimicking 3D physiological environments, sometimes referred to as “organ-on-a-chip” are known (e.g., PCT/US2009/050830, PCT/US2012/068766, and PCT/US2012/068461), but none of these platforms provides a level of throughput or compatibility with standard liquid handling and plate reading systems that are desirable in many biotechnology and pharmaceutical applications.
It is desirable to obviate or mitigate one or more of the above deficiencies.